Switching to Weekly Lonapegsomatropin from Daily Somatropin in Children with Growth Hormone Deficiency: The fliGHt Trial.

INTRODUCTION: The phase 3 fliGHt Trial evaluated the safety and tolerability of once-weekly lonapegsomatropin, a long-acting prodrug, in children with growth hormone deficiency (GHD) who switched from daily somatropin therapy to lonapegsomatropin. METHODS: This multicenter, open-label, 26-week phase 3 trial took place at 28 sites across 4 countries (Australia, Canada, New Zealand, and the USA). The trial enrolled 146 children with GHD, 143 of which were previously treated with daily somatropin. All subjects received once-weekly lonapegsomatropin 0.24 mg human growth hormone/kg/week. The primary outcome measure was safety and tolerability of lonapegsomatropin over 26 weeks. Secondary outcome measures assessed annualized height velocity (AHV), height standard deviation score (SDS), and IGF-1 SDS at 26 weeks. RESULTS: Subjects had a mean prior daily somatropin dose of 0.29 mg/kg/week. Treatment-emergent adverse events (AEs) reported were similar to the published AE profile of daily somatropin therapies. After switching to lonapegsomatropin, the least-squares mean (LSM) AHV was 8.7 cm/year (95% CI: 8.2, 9.2) at Week 26 and LSM height SDS changed from baseline to Week 26 of +0.25 (95% CI: 0.21, 0.29). Among switch subjects, the LSM for average IGF-1 SDS was sustained at Weeks 13 and 26, representing an approximate 0.7 increase from baseline (prior to switching from daily somatropin therapy). Patient-reported outcomes indicated a preference for weekly lonapegsomatropin among both children and their parents. CONCLUSIONS: Lonapegsomatropin treatment outcomes were as expected across a range of ages and treatment experiences. Switching to lonapegsomatropin resulted in a similar AE profile to daily somatropin therapy.

Alterations of the GH/IGF-I Axis and Gut Microbiome after Traumatic Brain Injury: A New Clinical Syndrome?

CONTEXT: Pituitary dysfunction with abnormal growth hormone (GH) secretion and neurocognitive deficits are common consequences of traumatic brain injury (TBI). Recognizing the comorbidity of these symptoms is of clinical importance; however, efficacious treatment is currently lacking. EVIDENCE ACQUISITION: A review of studies in PubMed published between January 1980 to March 2020 and ongoing clinical trials was conducted using the search terms "growth hormone," "traumatic brain injury," and "gut microbiome." EVIDENCE SYNTHESIS: Increasing evidence has implicated the effects of TBI in promoting an interplay of ischemia, cytotoxicity, and inflammation that renders a subset of patients to develop postinjury hypopituitarism, severe fatigue, and impaired cognition and behavioral processes. Recent data have suggested an association between abnormal GH secretion and altered gut microbiome in TBI patients, thus prompting the description of a hypothesized new clinical syndrome called "brain injury associated fatigue and altered cognition." Notably, these patients demonstrate distinct characteristics from those with GH deficiency from other non-TBI causes in that their symptom complex improves significantly with recombinant human GH treatment, but does not reverse the underlying mechanistic cause as symptoms typically recur upon treatment cessation. CONCLUSION: The reviewed data describe the importance of alterations of the GH/insulin-like growth factor I axis and gut microbiome after brain injury and its influence in promoting neurocognitive and behavioral deficits in a bidirectional relationship, and highlight a new clinical syndrome that may exist in a subset of TBI patients in whom recombinant human GH therapy could significantly improve symptomatology. More studies are needed to further characterize this clinical syndrome.

Prevalence of adrenal insufficiency following systemic glucocorticoid therapy in infants with hemangiomas.

OBJECTIVE: To determine the prevalence of adrenal insufficiency in infants with hemangiomas following treatment with systemic glucocorticoids (GCs). DESIGN: Prospective study for 18 months. SETTING: Hemangioma and vascular malformation center at a tertiary care children's hospital. PATIENTS: Sixteen infants with hemangiomas had an adrenal axis evaluation as soon as possible following the completion of GC therapy. Ten healthy control infants were also evaluated for comparison. INTERVENTIONS: Prednisolone at a starting dose of 2 to 3 mg/kg/d for 4 weeks, followed by a tapering period. The mean duration of GC treatment was 7.2 months. MAIN OUTCOME MEASURE: Prevalence of adrenal insufficiency in GC-treated subjects as assessed by a combination low-dose/high-dose corticotropin stimulation test. RESULTS: Subjects underwent corticotropin testing at a mean of 13 days after the completion of therapy. Only 1 of the 16 GC-treated infants (6%) had adrenal insufficiency. This subject was tested 1 day after GC treatment was stopped, and results from retesting 3 months later were normal. All control subjects had normal adrenal function. CONCLUSION: Infants with hemangiomas are at low risk of adrenal insufficiency following the completion of GC therapy, as used in our hemangioma center.